Peripheral blood NK bright cells are augmented in breast cancer patients non-reaching pathologic complete response to antibody anti HER2+-based therapy

Ayelén Ivana Pesce Viglietti¹, María Belén Bordignon¹, Alexis Ostinelli², Florencia Perazzo³, Manglio Miguel Rizzo⁴, Federico Coló², Gabriel Crimi³, Ignacio Mc Lean4, Pablo Mandó³, Estrella Mariel Levy¹, Victoria Costanzo², Sergio Rivero²



HER2+ breast cancer (BC) patients are treated with neoadjuvant therapy with trastuzumab and pertuzumab, both anti-HER2 antibodies. In this context, NK cells could play a fundamental role due to their ability to perform ADCC and secrete cytokines such as IFN-γ. We were interested in characterizing peripheral blood (PB) NK cells in BC patients compared to those from healthy donors (HD). Also, we wanted to determine if the peripheral immune profile is associated with the response to treatment with anti-HER2 antibodies. To do this, we analyzed by FACS 10 NK cell receptors (CD57, NKp30, NKp44, CD16, NKG2A, CD25, NKG2C, CD16, PD-L1, and TIM-3) on PBMC of 49 patients diagnosed before trastuzumab+pertuzumab therapy and 23 HD. Patients presented a higher percentage of NK dim compared to HD (95% vs 91%, p=0.0022), and also showed a higher proportion of NK PD-L1+cells (4.13% vs 1.8%, p=0.0069). Despite the low number of patients non-reaching pathologic complete response (5/37), it was found that they present a higher concentration of NK bright cells in PB (16 cells/µl vs 10 cells/µl, p=0.0161). Moreover, those patients with lymph node involvement (36/47) presented a higher percentage of NK cells than those without lymph node involvement (11.74% vs 8.57%, p = 0.026). These preliminary data exhibit several characteristics in HER2+ patients that could be associated with therapy response in the future. Currently, patient recruitment and functional tests continue.